Device with biological tissue scaffold for percutaneous closure of an intracardiac defect and methods thereof

ABSTRACT

The invention provides an intracardiac occluder, which has biological tissue scaffolds as occlusion shells, for the percutaneous transluminal treatment of an intracardiac defect. The intracardiac occluder includes a proximal support structure supporting the proximal occlusion shell and a distal support structure supporting the distal occlusion shell. In one embodiment, biological tissue derived from the tunica submucosa layer of the porcine small intestine forms the occlusion shells.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application incorporates by reference, and claims priorityto and the benefit of, U.S. provisional application serial No.60/385,274, which was filed Jun. 3, 2002.

TECHNICAL FIELD

[0002] The invention generally relates to devices and related methodsfor treating intracardiac defects. More particularly, the inventionprovides an intracardiac occluder with a biological tissue scaffold, andrelated methods, for the percutaneous closure of intracardiac defects.

BACKGROUND

[0003] The human heart is divided into four compartments or chambers.The left and right atria are located in the upper portion of the heartand the left and right ventricles are located in the lower portion ofthe heart. The left and right atria are separated from each other by amuscular wall, the intraatrial septum, while the ventricles areseparated by the intraventricular septum.

[0004] Either congenitally or by acquisition, abnormal openings, holes,or shunts can occur between the chambers of the heart or the greatvessels, causing blood to flow therethrough. Such deformities areusually congenital and originate during fetal life when the heart formsfrom a folded tube into a four chambered, two unit system. Thedeformities result from the incomplete formation of the septum, ormuscular wall, between the chambers of the heart and can causesignificant problems. Ultimately, the deformities add strain on theheart, which may result in heart failure if they are not corrected.

[0005] One such deformity or defect, a patent foramen ovale, is apersistent, one-way, usually flap-like opening in the wall between theright atrium and left atrium of the heart. Since left atrial pressure isnormally higher than right atrial pressure, the flap typically staysclosed. Under certain conditions, however, right atrial pressure exceedsleft atrial pressure, creating the possibility for right to leftshunting that can allow blood clots to enter the systemic circulation.This is particularly worrisome to patients who are prone to formingvenous thrombus, such as those with deep vein thrombosis or clottingabnormalities.

[0006] Nonsurgical (i.e., percutaneous) closure of patent foramenovales, as well as similar intracardiac defects such as atrial septaldefects, ventricular septal defects, and left atrial appendages, ispossible using a variety of mechanical closure devices. These devices,which allow patients to avoid the potential side effects oftenassociated with standard anticoagulation therapies, typically consist ofa metallic structural framework that is combined with a syntheticscaffold material. The synthetic scaffold material encourages ingrowthand encapsulation of the device. Current devices typically utilize apolyester fabric, expanded polytetrafluoroethylene (ePTFE), Ivalon®, ora metal mesh as the synthetic scaffold material. Such devices suffer,however, from several disadvantages, including thrombus formation,chronic inflammation, and residual leaks.

SUMMARY OF THE INVENTION

[0007] The present invention provides a device for occludingintracardiac defects. The device includes a biological tissue scaffold,as opposed to a synthetic scaffold (e.g., a polyester fabric, ePTFE,Ivalon®, or a metal mesh) as presently used by devices known in the art.In a preferred embodiment, the biological tissue scaffold is fabricatedfrom collagen. In one embodiment, a specific type of biological tissue,derived from the tunica submucosa layer of the porcine small intestine,forms the tissue scaffold. As a result of this structure, theaforementioned disadvantages associated with the devices known in theart are minimized or eliminated.

[0008] In one aspect, the invention provides an intracardiac occluderfor percutaneous transluminal treatment of an intracardiac defect. Theintracardiac occluder includes a proximal support structure supporting aproximal occlusion shell and a distal support structure supporting adistal occlusion shell. The distal support structure is coupled to theproximal support structure and at least one of the occlusion shellsincludes a biological tissue scaffold.

[0009] Various embodiments of this aspect of the invention include thefollowing features. The biological tissue scaffold may be a purifiedbioengineered type 1 collagen that may be derived from a tunicasubmucosa layer of a porcine small intestine. Further, in oneembodiment, at least one of the support structures includes a corrosionresistant metal. Alternatively, at least one of the support structuresincludes a bioresorbable polymer or a biodegradable polymer. In yetanother embodiment, the proximal support structure includes a pluralityof outwardly extending proximal arms and the distal support structureincludes a plurality of outwardly extending distal arms.

[0010] In another aspect, the invention provides a method forpercutaneous transluminal treatment of an intracardiac defect in apatient. The method includes providing an intracardiac occluder asdescribed above, positioning the intracardiac occluder proximate theintracardiac defect, and engaging the intracardiac defect with theintracardiac occluder to substantially occlude the intracardiac defect.

[0011] In one embodiment of this aspect of the invention, theintracardiac defect is engaged by positioning the proximal occlusionshell and the distal occlusion shell on different sides of theintracardiac defect. The intracardiac defect may be, for example, apatent foramen ovale, an atrial septal defect, a ventricular septaldefect, or a left atrial appendage.

[0012] In yet another aspect, the invention provides a method for makingan intracardiac occluder for the percutaneous transluminal treatment ofan intracardiac defect. The method includes providing an overall supportstructure and first and second biological tissue scaffolds. The overallsupport structure includes a proximal support structure and a distalsupport structure. The method further includes coupling the firstbiological tissue scaffold to the proximal support structure andcoupling the second biological tissue scaffold to the distal supportstructure. In various embodiments of this aspect of the invention, thebiological tissue scaffolds are sewn, laminated, or glued to the supportstructures.

[0013] The foregoing and other objects, aspects, features, andadvantages of the invention will become more apparent from the followingdescription and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] In the drawings, like reference characters generally refer to thesame parts throughout the different views. Also, the drawings are notnecessarily to scale, emphasis instead generally being placed uponillustrating the principles of the invention.

[0015]FIG. 1 is a cutaway view of a heart illustrating an intracardiacdefect.

[0016]FIG. 2A is a top plan view of an intracardiac occluder accordingto an illustrative embodiment of the invention.

[0017]FIG. 2B is a cross-sectional view of the illustrative intracardiacoccluder of FIG. 2A.

[0018]FIG. 3A is a top plan view of an intracardiac occluder accordingto another illustrative embodiment of the invention.

[0019]FIG. 3B is a side view of the illustrative intracardiac occluderof FIG. 3A.

[0020]FIG. 4 is a perspective view of an intracardiac occluder accordingto another illustrative embodiment of the invention.

[0021] FIGS. 5A-5E illustrate the stages, according to an illustrativeembodiment of the invention, for delivering an intracardiac occluder toan anatomical site in the body of a patient.

[0022]FIG. 6A illustrates the results from occluding an intracardiacdefect with an intracardiac occcluder known in the art, 30-days afterdelivery of the intracardiac occluder.

[0023]FIG. 6B illustrates the results from occluding an intracardiacdefect with an intracardiac occluder according to the invention, 30-daysafter delivery of the intracardiac occluder.

[0024]FIG. 7A illustrates the results from occluding an intracardiacdefect with an intracardiac occcluder known in the art, 90-days afterdelivery of the intracardiac occluder.

[0025]FIG. 7B illustrates the results from occluding an intracardiacdefect with an intracardiac occcluder according to the invention,90-days after delivery of the intracardiac occluder.

DETAILED DESCRIPTION OF THE INVENTION

[0026] The present invention provides an intracardiac occluder for therepair of intracardiac defects, such as, for example, a patent foramenovale, an atrial septal defect, a ventricular septal defect, and leftatrial appendages. The intracardiac occluder includes a structuralframework and a biological tissue scaffold adhered thereto.

[0027]FIG. 1 depicts a cutaway view of a heart 100. The heart 100includes a septum 104 that divides a right atrium 108 from a left atrium112. The septum 104 includes a septum primum 116, a septum secundum 120,and an exemplary intracardiac defect 124, which is to be corrected bythe intracardiac occluder of the present invention, between the septumprimum 116 and the septum secundum 120. Specifically, a patent foramenovale 124 is shown as an opening through the septum 104. The patentforamen ovale 124 provides an undesirable fluid communication betweenthe right atrium 108 and the left atrium 112. Under certain conditions,a large patent foramen ovale 124 in the septum 104 would allow for theshunting of blood from the right atrium 108 to the left atrium 112. Ifthe patent foramen ovale 124 is not closed or obstructed in some manner,a patient is placed at high risk for an embolic stroke.

[0028]FIG. 2A depicts an intracardiac occluder 10 according to anillustrative embodiment of the invention. As shown, the intracardiacoccluder 10 includes a proximal occlusion shell 18 (i.e., an occlusionshell that is closest to an operator of the intracardiac occluder 10(e.g., a physician)), an opposite distal occlusion shell 20, and anoverall support structure 16. The overall support structure 16 includesa proximal support structure 24, for supporting the proximal occlusionshell 18, and a distal support structure 34, for supporting the distalocclusion shell 20. In one embodiment, both the proximal supportstructure 24 and the distal support structure 34 include outwardlyextending arms to support each of their respective occlusion shells 18,20. As shown in FIG. 2A, for example, the proximal support structure 24includes four outwardly extending arms 26 and the distal supportstructure 34 similarly includes four outwardly extending arms 36. In oneembodiment, each outwardly extending arm is resiliently biased as aresult of including three or more resilient coils 43 radially spacedfrom a center point 45. Alternatively, other resilient supportstructures could be used. In one embodiment, the eight arms 26, 36 aremechanically secured together by wire 52. Alternatively, other means,such as, for example, laser welding, may be used to secure the eightarms 26, 36 together. A cross-sectional view of the intracardiacoccluder 10 illustrated in FIG. 2A, showing four arms 26, 36, isdepicted in FIG. 2B.

[0029]FIGS. 3A and 3B depict an intracardiac occluder 10′ according toanother illustrative embodiment of the invention. An overall supportstructure 16′ forms a clip and includes a proximal support structure24′, for supporting a proximal occlusion shell 18′, and a distal supportstructure 34′, for supporting a distal occlusion shell 20′.

[0030] An intracardiac occluder 10″ according to yet anotherillustrative embodiment of the invention is illustrated in FIG. 4.Again, an overall support structure 16″ forms a clip and includes aproximal support structure 24″, for supporting a proximal occlusionshell 18″, and a distal support structure 34″, for supporting a distalocclusion shell 20″.

[0031] Alternatively, the overall support structure 16 may assume anyshape or configuration to form the proximal support structure 24 and thedistal support structure 34.

[0032] In one embodiment, the overall support structure 16 is fabricatedfrom a corrosion resistant metal, such as, for example, stainless steel,nitinol, or a nickel-cobalt-chromium-molybdenum alloy (e.g., MP35N).Alternatively, in other embodiments, the overall support structure 16 isfabricated from bioresorbable or biodegradeable polymers.

[0033] In accordance with the present invention, the occlusion shells18, 20, which are attached, as described below, to the proximal supportstructure 24 and the distal support structure 34, respectively, are madefrom a biological tissue scaffold. In a preferred embodiment, the tissuescaffold is fabricated from collagen. In one embodiment, a purified(acellular) bioengineered type 1 collagen derived from the tunicasubmucosa layer of the porcine small intestine forms the tissuescaffold. More specifically, the tunica submucosa layer, referred tohereinafter as the Intestinal Collagen Layer (“ICL”), is separated ordelaminated from the other layers of the porcine small intestine (i.e.,the tunica muscularis and the tunica mucosa) by any method known in theart. For example, a Bitterling sausage casing machine is used to performthe separation. Once mechanically separated from the other layers, theICL is, in one embodiment, chemically cleaned to remove debris and othersubstances, other than collagen. For example, the ICL is soaked in abuffer solution at 4 degrees Celsius without the use of any detergents,or, alternatively, in a second embodiment, it is soaked with NaOH ortrypsin. Other cleaning techniques known to those skilled in the art mayalso be used. After cleaning, the ICL is decontaminated. Anysterilization system for use with collagen, as known in the art, may beused. For example, a dilute peracetic acid solution, gammasterilization, or electron-beam sterilization is used to decontaminatethe ICL.

[0034] Alternatively, collagenous tissue from the fascia lata,pericardium, or dura matter of pigs or other mammalian sources, such as,for example, cows or sheep, may form the tissue scaffold. Additionally,in making the occlusion shells 18, 20, two or more collagen layers maybe bonded together and then cross-linked to produce a biocompatiblematerial capable of being remodeled by the host cells.

[0035] In one embodiment, the biological tissue scaffold is non-porousand prevents the passage of fluids that are intended to be retained bythe implantation of the intracardiac occluder 10. In another embodiment,heparin is ionically or covalently bonded to the biological tissuescaffold to render it non-thrombogenic. In yet other embodiments,proteins or cells are applied to the biological tissue scaffold torender it non-thrombogenic and/or accelerate the healing process. Growthfactors may also be applied to the biological tissue scaffold toaccelerate the healing process.

[0036] Referring again to FIG. 2A, the occlusion shells 18, 20 are, inone embodiment, generally square in shape. Alternatively, the occlusionshells 18, 20 may assume other shapes. The biological tissue scaffoldforming the occlusion shells 18, 20 is strong and flexible. Theocclusion shells 18, 20 therefore easily attach to the overall supportstructure 16 and, as explained below, withstand sheath delivery to ananatomical site in the body of a patient. In one embodiment, theocclusion shells 18, 20 are sewn, as at 22A, 22B, with any commonly usedsuture material (e.g., a polyester suture) that threads through thedistal ends 54 of the respective arms 26, 36 of the proximal supportstructure 24 and the distal support structure 34. Alternatively, theocclusion shells 18, 20 are laminated, glued, or attached by, forexample, hooks or thermal welding to the proximal support structure 24and the distal support structure 34. In yet another embodiment, theocclusion shells 18, 20 are laminated to the overall support structure16 and, additionally, to one another, such that the overall supportstructure 16 is encapsulated entirely within the occlusion shells 18,20.

[0037] FIGS. 5A-5E depict the stages for delivering the intracardiacoccluder 10, according to an illustrative embodiment of the invention,percutaneously to an anatomical site in the body of a patient. Referringto FIG. 5A, a sheath 190 is first inserted into the intracardiac defect186 as is typically performed by one skilled in the art. Theintracardiac occluder 10 is then loaded into the lumen 188 of the sheath190 and advanced throughout the lumen 188 until positioned at the distalend 192 of the sheath 190. Referring to FIG. 5B, the distal occlusionshell 20 of the intracardiac occluder 10 is released into the distalheart chamber 191 through the distal end 192 of the sheath 190. Thedistal occlusion shell 20 opens automatically and resiliently. Thesheath 190 is then pulled back into the proximal heart chamber 193, asillustrated in FIG. 5C, to seat the distal occlusion shell 20 againstthe distal wall surface 194 of the intracardiac defect 186. Theintracardiac defect 186 is thereby occluded from the distal side. Asshown in FIG. 5D, the sheath 190 is then further withdrawn a sufficientdistance to allow the proximal occlusion shell 18 to be released fromthe distal end 192 of the sheath 190. The proximal occlusion shell 18opens automatically and resiliently to lie against the proximal surface196 of the intracardiac defect 186, occluding the intracardiac defect186 from the proximal side. The sheath 190 is then withdrawn from thepatient's body, leaving behind the opened intracardiac occluder 10. Asshown in FIG. 5E, the occlusion shells 18, 20 are positioned on eitherside of the intracardiac defect 186 and the intracardiac occluder 10 ispermanently implanted within the body of the patient.

[0038] FIGS. 6A-6B and 7A-7B depict comparative 30-day and 90-dayresults, respectively, for the percutaneous closures of interventionallycreated intracardiac defects in sheep. Specifically, FIGS. 6A and 7Adepict the 30-day and 90-day results, respectively, when an exemplaryintracardiac occluder known in the art, whose occlusion shells werefabricated from a polyester fabric (i.e., a synthetic scaffoldmaterial), is used to occlude the intracardiac defect. FIGS. 6B and 7Bdepict the 30-day and 90-day results, respectively, when theintracardiac occluder 10 of the instant invention, whose occlusionshells 18, 20 were fabricated from ICL, is used to occlude theintracardiac defect.

[0039] As shown, the biological tissue scaffold of the intracardiacoccluder 10 of the present invention increases the rate of tissueingrowth and, consequently, decreases the time needed to completelyclose the intracardiac defect. Specifically, referring now to FIG. 7B,the intracardiac occluder 10 of the present invention is barely visibleafter 90-days. The surrounding tissue ingrowth nearly completelyenvelopes the intracardiac occluder 10. In comparison, referring now toFIG. 7A, the exemplary intracardiac occluder known in the art is stillclearly visible after the same period of time.

[0040] As also shown, the intracardiac occluder 10 of the presentinvention naturally adheres to, and seals completely along, the edge ofthe intracardiac defect in a manner that is much improved from theexemplary intracardiac occluder known in the art. Additionally, in oneembodiment, the biological tissue scaffold of the intracardiac occluder10 of the present invention is non-porous. As a result, the intracardiacoccluder 10 decreases the likelihood of fluid (e.g., blood) leakagethrough the opening.

[0041] Further advantages to the intracardiac occluder 10 of the presentinvention, in comparison to known intracardiac occluders, includedecreased thrombogenicity, quicker endothelialization, superiorbiocompatibility, minimal foreign body reaction, decreased immunologicaland inflammatory responses, and no fibrosis.

[0042] Variations, modifications, and other implementations of what isdescribed herein will occur to those of ordinary skill in the artwithout departing from the spirit and the scope of the invention asclaimed. Accordingly, the invention is to be defined not by thepreceding illustrative description but instead by the spirit and scopeof the following claims.

What is claimed is:
 1. An intracardiac occluder for percutaneoustransluminal treatment of an intracardiac defect, comprising: a proximalsupport structure supporting a proximal occlusion shell; and a distalsupport structure, coupled to the proximal support structure, supportinga distal occlusion shell, wherein at least one of the occlusion shellscomprises a biological tissue scaffold.
 2. The occluder of claim 1,wherein the biological tissue scaffold comprises a purifiedbioengineered type 1 collagen.
 3. The occluder of claim 2, wherein thepurified bioengineered type 1 collagen is derived from a tunicasubmucosa layer of a porcine small intestine.
 4. The occluder of claim1, wherein at least one of the support structures comprises a corrosionresistant metal.
 5. The occluder of claim 1, wherein at least one of thesupport structures comprises a bioresorbable polymer.
 6. The occluder ofclaim 1, wherein at least one of the support structures comprises abiodegradable polymer.
 7. The occluder of claim 1, wherein the proximalsupport structure comprises a plurality of outwardly extending proximalarms and the distal support structure comprises a plurality of outwardlyextending distal arms.
 8. A method for percutaneous transluminaltreatment of an intracardiac defect in a patient, comprising: providingan intracardiac occluder, comprising: a proximal support structuresupporting a proximal occlusion shell; and a distal support structure,coupled to the proximal support structure, supporting a distal occlusionshell, wherein at least one of the occlusion shells comprises abiological tissue scaffold; positioning the intracardiac occluderproximate the intracardiac defect; and engaging the intracardiac defectwith the intracardiac occluder to substantially occlude the intracardiacdefect.
 9. The method of claim 8, wherein engaging the intracardiacdefect comprises positioning the proximal occlusion shell and the distalocclusion shell on different sides of the intracardiac defect.
 10. Themethod of claim 8, wherein the intracardiac defect is a patent foramenovale.
 11. The method of claim 8, wherein the intracardiac defect is anatrial septal defect.
 12. The method of claim 8, wherein theintracardiac defect is a ventricular septal defect.
 13. The method ofclaim 8, wherein the intracardiac defect is a left atrial appendage. 14.A method for making an intracardiac occluder for percutaneoustransluminal treatment of an intracardiac defect, comprising: providingan overall support structure comprising a proximal support structure anda distal support structure; providing first and second biological tissuescaffolds; coupling the first biological tissue scaffold to the proximalsupport structure; and coupling the second biological tissue scaffold tothe distal support structure.
 15. The method of claim 14, whereincoupling the biological tissue scaffolds comprises sewing the biologicaltissue scaffolds to the support structures.
 16. The method of claim 14,wherein coupling the biological tissue scaffolds comprises laminatingthe biological tissue scaffolds to the support structures.
 17. Themethod of claim 14, wherein coupling the biological tissue scaffoldscomprises gluing the biological tissue scaffolds to the supportstructures.